What are the causes and correction methods for metabolic alkalosis?

Metabolic Alkalosis: Causes and Correction

Primary Causes

Metabolic alkalosis results from either loss of fixed acid or net accumulation of bicarbonate, with the kidney's inability to excrete excess bicarbonate being essential for maintenance of the alkalosis. 1

Chloride-Responsive Alkalosis (Urinary Cl <20 mEq/L)

• Gastrointestinal losses: Vomiting or nasogastric suction causes hydrogen ion loss and volume contraction 2, 1
• Diuretic therapy: Loop and thiazide diuretics are among the most common causes, creating chloride depletion, hypokalemia, and volume contraction 2, 3
• Volume contraction states: Any condition causing chloride and volume depletion will maintain alkalosis 2, 4

Chloride-Resistant Alkalosis (Urinary Cl >20 mEq/L)

• Mineralocorticoid excess: Primary hyperaldosteronism or secondary hyperaldosteronism from heart failure 2, 5
• Bartter and Gitelman syndromes: Genetic salt-losing tubulopathies characterized by hypokalemic metabolic alkalosis, normotension, and elevated renin/aldosterone despite volume depletion 2, 1
• Excess alkali administration: Oral or parenteral bicarbonate intake 1, 5

Maintenance Factors

The kidney normally eliminates excess bicarbonate efficiently, but several factors impair this mechanism and perpetuate alkalosis 1:

• Volume contraction and hypochloremia (most common) 2, 4
• Hypokalemia (potassium depletion) 2, 4
• Reduced glomerular filtration rate 1
• Aldosterone excess 1, 3
• Elevated arterial CO2 1

Diagnostic Approach

Measure urinary chloride concentration to classify the alkalosis type, which directly guides treatment strategy. 2

Initial Assessment

• Check urinary chloride: <20 mEq/L indicates chloride-responsive; >20 mEq/L indicates chloride-resistant alkalosis 2
• Assess volume status: Determine if patient is hypovolemic, euvolemic, or hypervolemic 4
• Measure serum electrolytes: Identify hypokalemia (<3.5 mEq/L), hypochloremia, and bicarbonate elevation 2, 4

For Chloride-Resistant Alkalosis

• Measure plasma renin and aldosterone: Both markedly elevated suggests Bartter/Gitelman syndrome or secondary hyperaldosteronism 2
• Check urinary calcium: High in Bartter syndrome, low in Gitelman syndrome 2
• Assess fractional excretion of chloride: >0.5% in Bartter syndrome despite volume depletion 2
• Consider genetic testing: For SLC12A1 (Bartter type 1) or KCNJ1 (Bartter type 2) mutations if syndrome suspected 2
• Obtain renal ultrasound: May show bilateral nephrocalcinosis in Bartter syndrome 2

Treatment Strategies

Chloride-Responsive Alkalosis (Most Common)

The cornerstone of treatment is correction of volume and chloride deficits with normal saline, along with potassium chloride supplementation. 2, 4

Fluid and Electrolyte Replacement

• Administer normal saline (0.9% NaCl): Restores volume and provides chloride, allowing the kidney to excrete excess bicarbonate 4
• Potassium chloride supplementation: 20-60 mEq/day to maintain serum potassium 4.5-5.0 mEq/L 2
• Critical point: Use only potassium chloride, never potassium citrate or potassium bicarbonate, as these worsen alkalosis 2
• Correct hypokalemia to >3.5 mmol/L before addressing other aspects 2

Diuretic Management

• Discontinue or reduce diuretic doses if clinically feasible 2
• Switch to longer-acting loop diuretics or add potassium-sparing diuretics 2

Chloride-Resistant Alkalosis

Potassium-Sparing Diuretics (First-Line)

Amiloride is the most effective potassium-sparing diuretic for metabolic alkalosis, providing improvement in edema/hypertension while countering hypokalemia. 2

• Amiloride: Start 2.5 mg daily, titrate up to 5 mg daily 2
• Spironolactone: Start 25 mg daily, titrate up to 50-100 mg daily 2
• Avoid combining with ACE inhibitors without close monitoring due to hyperkalemia risk 2
• Contraindicated in significant renal dysfunction or existing hyperkalemia 2

Bartter/Gitelman Syndrome Specific Treatment

• Sodium chloride supplementation: 5-10 mmol/kg/day 2, 6
• Potassium chloride supplementation: For potassium repletion 2, 6
• NSAIDs (indomethacin or ibuprofen): Reduce prostaglandin-mediated salt wasting in symptomatic patients 2
• Gastric acid inhibitors: Must be used concurrently with NSAIDs to prevent GI complications 2

Heart Failure Patients with Diuretic-Induced Alkalosis

Acetazolamide 500 mg IV as a single dose is effective in heart failure patients with adequate kidney function, causing rapid fall in serum bicarbonate with normalization of pH. 2, 7

Acetazolamide Mechanism and Use

• Mechanism: Inhibits carbonic anhydrase in the kidney, causing renal loss of bicarbonate along with sodium, water, and potassium 7
• Dosing: 500 mg IV single dose 2
• Requirements: Adequate kidney function (avoid in severe renal dysfunction) 2
• Caution: Exercise caution when combining with other diuretics due to increased risk of dehydration and severe electrolyte imbalances 2
• Avoid furosemide unless hypervolemia, hyperkalemia, or renal acidosis present, as loop diuretics perpetuate alkalosis 2

Aldosterone Antagonist Addition

• Add spironolactone to diuretic regimen for appropriate management of circulatory failure 2, 3

Severe or Refractory Metabolic Alkalosis

In anuric patients or those with refractory metabolic alkalosis and concurrent renal failure, hemodialysis with low-bicarbonate/high-chloride dialysate is the treatment of choice. 2, 6

Renal Replacement Therapy

• Hemodialysis or CRRT with low-bicarbonate dialysate: Primary treatment when kidneys cannot excrete excess bicarbonate 6
• CRRT preferred in critically ill patients: Allows more gradual correction and better hemodynamic stability 6
• Adjust dialysate composition: Avoid supra-physiologic bicarbonate levels that worsen alkalosis 6

Direct Acid Administration (Rarely Needed)

• Dilute hydrochloric acid (0.1-0.2 N): Reserved for severe cases with hepatic dysfunction where ammonium chloride cannot be used; must be given via central venous catheter 8
• Contraindication: Sodium bicarbonate or alkalinization strategies are contraindicated and will worsen alkalosis 2

Special Situation: Alcohol Starvation State with Anuria

• Initiate renal replacement therapy with low-bicarbonate dialysate as primary treatment 6
• Administer dextrose-containing IV fluids (D5W or D10W): Suppresses ketogenesis 6
• Give thiamine 100 mg IV before glucose: Prevents Wernicke's encephalopathy 6
• Aggressively replete potassium and phosphate: Monitor for refeeding syndrome 6

Monitoring Parameters

• Arterial blood gases: Every 2-4 hours during active treatment 6
• Serum electrolytes (Na, K, Cl, HCO3): Every 2-4 hours during active treatment 6
• Adjust therapy based on clinical response and laboratory parameters 2

Common Pitfalls to Avoid

• Never use potassium citrate or potassium bicarbonate for potassium repletion—these worsen metabolic alkalosis; use only potassium chloride 2
• Do not overlook Bartter or Gitelman syndrome in euvolemic patients with unexplained metabolic alkalosis, especially with history of polyhydramnios and premature birth 2
• Avoid potassium-sparing diuretics in significant renal dysfunction or existing hyperkalemia 2
• Do not use loop diuretics unless specific indications (hypervolemia, hyperkalemia, renal acidosis) exist, as they perpetuate alkalosis 2